In recent years, microRNAs (miRs, miRNAs) have emerged as an important novel class of regulatory RNA, which has profound impact on a wide array of biological processes. These small (typically 18-24 nucleotides long) non-coding RNA molecules can modulate protein expression patterns by promoting RNA degradation, inhibiting mRNA translation, and also affecting gene transcription. miRs play pivotal roles in diverse processes such as development and differentiation, control of cell proliferation, stress response and metabolism. There are currently about 850 known human miRs. The expression of many miRs was found to be altered in numerous types of human cancer, and in some cases strong evidence has been put forward in support of the conjecture that such alterations may play a causative role in tumor progression. MicroRNA expression is highly tissue specific and informative for identification of tumor tissue origin.
Mesothelioma is a tumor that occurs in the mesothelium that covers the surface of the pleura, pericardium and peritoneum that respectively envelop the organs of the chest cavity such as the lungs and heart, and abdominal organs such as the digestive tract and liver. In the case of diffuse pleural mesothelioma, chest pain is caused by invasion of the intercostal nerves on the side of the chest wall pleura, and respiratory and circulatory disorders may occur due to tumor growth and accumulation of pleural fluid in the pleura on the organ side. There is eventually proliferation into the adjacent mediastinal organs, progressing to direct invasion of the heart or development into the abdominal cavity by means of the diaphragm, or there may be development outside the chest cavity as a result of additional lymphatic or circulatory metastasis.
Numerous different classifications of the clinical disease stages have been used for mesothelioma, and since the methods for classifying the disease stage used differ, previous therapeutic reports on mesothelioma have encountered difficulties when comparing the results of treatment (Nakano, Respiration, Vol. 18, No. 9, pp. 916-925, 1999). In addition, malignant mesothelioma has a causative relationship with exposure to asbestos, and this has also been demonstrated in animal experiments (Tada, Journal of Clinical and Experimental Medicine (March Supplement), “Respiratory Diseases”, pp. 406-408, 1999). Asbestos that has been inhaled into the respiratory tract reaches a location directly beneath the pleura where a tumor eventually develops due to chronic irritation for at least about 20 years, and this tumor spreads in a thin layer over the entire surface of the pleura. Consequently, although malignant mesothelioma is classified as an asbestos-related disease, not all malignant mesothelioma is caused by asbestos, and well-documented exposure is only observed in about half of all patients. Malignant pleural mesothelioma is resistant to treatment, associated with an extremely poor prognosis, and requires that countermeasures be taken immediately (Nakano, Respiration, Vol. 18, No. 9, pp. 916-925, 1999).
The prognosis for malignant mesothelioma is influenced by the stage of the disease. Surgery, as well as adjuvant immunological treatments (e.g., interferon or interleukin) can be effective treatment, but only in the rare event of an early stage diagnosis.
When dealing with the possibility of a mesothelioma in the pleura or the peritoneum few differential indications should be considered. Both the pleura and the peritoneum can have secondary malignancies with primaries at different rates, hence differentiation between mesothelioma and secondary malignancy or another primary from different source is important. Pathological diagnosis can have significant inter-observer variability, and in the absence of specific markers mesothelioma is difficult to identify from other epithelial cancers.
Lung cancer is one of the most common cancers and has become a predominant cause of cancer-related death throughout the world. Scientists strive to explore biomarkers and their possible role in the diagnosis, treatment and prognosis of specific lung cancers.
Making the correct diagnosis and specifically the distinction between lung squamous carcinoma and other Non Small Cell Lung Carcinoma (NSCLC) such as but not limited to lung adenocarcinoma, has practical importance for choice of therapy. Severe or fatal hemorrhage is a black box warning for lung squamous carcinoma patients undergoing bevacizumab (Avastin) therapy. To-date there is no objective standardized test for differentiating squamous from non squamous NSCLC.
The search for biomarkers for the early detection and accurate diagnosis of various NSCLC has met with little success. Much emphasis has been placed on the discovery and characterization of a unique tumor marker. However, no marker has been identified that has adequate sensitivity or specificity to be clinically useful, although a combination of multiple markers has been shown to increase diagnostic accuracy.
There is an unmet need for specific and accurate markers associated with specific types of cancers.